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Biomedical subjects

D S Milliner

Publications and source records attributed to D S Milliner.

At least 19 recordsLinked to original sources
PubMed2001

(L)-2-oxothiazolidine-4-carboxylate in the treatment of primary hyperoxaluria type 1.

OBJECTIVE: To evaluate the short-term efficacy of (l)-2-oxothiaolidine-4-carboxylate (OTZ, which reduces urinary oxalate excretion in normal subjects) in the treatment of primary hyperoxaluria type 1 (PH1) in a phase II study. PATIENTS AND METHODS: Two patients with PH1 received intravenous infusions of OTZ (100 mg/kg body weight for 2 h) given every 8 h for four doses. One patient also received a placebo treatment. Urine samples (24-h collections) were obtained before and during OTZ treatment and assayed for oxalate, citrate, creatinine, sulphate and pH. Daily blood samples were assayed for plasma oxalate and serum creatinine. RESULTS: Urinary oxalate excretion was unaffected by OTZ treatment. Plasma oxalate declined in both individuals with OTZ treatment, but the effect was small. Plasma cysteine was normal in one patient, rising from a mean (sd) of 36 (3.7) micromol/L before treatment to a peak of 141 micromol/L after OTZ, but was not detected in samples from the other patient. The ratio of oxalate to creatinine clearances was high in both patients, with mean values of 3.1 and 3.8. CONCLUSIONS: Treatment with OTZ did not lead to clinically significant changes in urinary oxalate excretion. The high clearance of oxalate in these patients suggests a substantial renal secretion of oxalate.

Calcium Oxalate↗
PubMed2001

Phenotypic expression of primary hyperoxaluria: comparative features of types I and II.

BACKGROUND: The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available. METHODS: Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation. RESULTS: PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03). CONCLUSION: The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.

Adolescent↗
PubMed2001

Two cases of non-O157:H7 Escherichia coli hemolytic uremic syndrome caused by urinary tract infection.

Escherichia coli serotype O157:H7 is a leading cause of diarrhea and hemolytic uremic syndrome (HUS). Because of the limitations of current diagnostic techniques, the prevalence of non-O157:H7 Shiga toxin-producing E coli strains is not known. We describe two patients with HUS in whom no E coli O157:H7 was demonstrable in stool cultures. On culture of the urine, the first patient was found to have E coli O113:H21 strain, and the second patient had E coli O6:H1 serotype. Shiga toxin production (stx2) by the O113:H21 isolate was confirmed. The first patient required 15 days of peritoneal dialysis and subsequently recovered renal function. At last follow-up, serum creatinine was 0.9 mg/dL. The second patient had preservation of renal function throughout the acute illness with serum creatinine of 0.5 mg/dL. The clinical presentation, bacteriology, course, and outcome as well as epidemiologic implications of the increasing number of patients with E coli urinary tract infections associated with HUS are discussed. These cases illustrate the need to investigate patients with nondiarrheal HUS for infection with Shiga toxin-producing E coli of the non-O157 strain variety.

Acute Kidney Injury↗
PubMed2001

Combined liver-kidney and kidney-alone transplantation in primary hyperoxaluria.

Combined liver-kidney and kidney-only transplantation outcomes in primary hyperoxaluria (PH) are described. Strategies for the selection of type and timing of transplantation and pretransplantation and posttransplantation management are reviewed. Records were reviewed for 16 patients with PH who received 9 liver-kidney and 10 kidney-only transplants. Plasma oxalate values declined from 61 +/- 42 micromol/L pretransplantation to 9 +/- 6 micromol/L 1 month after transplantation in liver-kidney transplant recipients and 92 +/- 19 to 9 +/- 5 micromol/L in kidney-only transplant recipients. In most liver-kidney transplant recipients, hyperoxaluria persisted for 6 to 18 months after transplantation. Follow-up was 3.5 +/- 4.1 years in liver-kidney and 4.5 +/- 6.3 years in kidney-alone transplant recipients. Patient survival rates were 78% for liver-kidney and 89% for kidney-only transplant recipients. No hepatic allografts were lost. Three of 9 liver-kidney and 6 of 10 kidney-alone transplants lost renal allograft function. In those with functioning kidneys, renal clearance was 45.1 +/- 19.5 mL/min/1.73 m(2) in liver-kidney transplant recipients and 49.5 +/- 26.1 mL/min/1.73 m(2) in kidney-only transplant recipients at last follow-up. Kaplan-Meier 1-, 2-, 3-, and 5-year renal allograft survival rates for patients undergoing transplantation after 1984 were 78%, 78%, 52%, and 52% in liver-kidney transplant recipients and 86%, 71%, 54%, and 36% in kidney-only transplant recipients. Simultaneous grafting of liver and kidney after the development of renal insufficiency is recommended for the majority of patients with PH type I (PH-I). Kidney-alone transplantation is recommended for those with pyridoxine-responsive type I disease because pharmacological therapy allows favorable management of oxalate production in this situation. Kidney-alone transplantation also is recommended for PH type II (PH-II). This disease is less severe than PH-I, and it is currently unknown whether liver transplantation will correct the metabolic defect responsible for PH-II.

Adolescent↗
PubMed2001

Chronic renal failure secondary to oxalate nephropathy: a preventable complication after jejunoileal bypass.

Enteric hyperoxaluria is a commonly seen adverse event after the jejunoileal bypass procedure. The increased concentration of urinary oxalate predisposes bypass patients to various renal complications such as nephrolithiasis and oxalate nephropathy. If not diagnosed and appropriately treated, these complications can lead to irreversible renal damage. We describe 3 patients in whom severe renal complications developed with irreversible compromise of renal function after a jejunoileal bypass. Patients who undergo a jejunoileal bypass require lifelong follow-up with close monitoring of their renal function. Marked decline in renal function mandates prompt investigation and aggressive intervention, including reversal of the jejunoileal bypass if necessary. Chronic renal failure secondary to oxalate nephropathy is preventable and treatable but may require conversion of a jejunoileal bypass to a more current form of bypass.

Aftercare↗
PubMed1999

Disseminated varicella infection in pediatric renal transplant recipients treated with mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is a new immune suppressive agent, effective in the prevention of acute rejection after renal transplantation. METHODS: The study was a retrospective review of records of pediatric renal transplant recipients from 1985 to the present. RESULTS: Since October 1995, the immune suppression protocol for pediatric renal transplant recipients at Mayo Eugenio Litta Children's Hospital has included MMF, prednisone, and cyclosporine A. During that time, 19 children and adolescents have received renal allografts, 17 of whom were seropositive for varicella antibody before transplantation, while 2 were seronegative. Varicella infection occurred in 3 of 19 patients (15.8%), all 3 of whom had serologically documented immunity to varicella virus before transplantation. All episodes occurred within 12 months of transplantation. All had generalized vesicular lesions without dermatomal distribution. None of the patients developed fever, respiratory, mucocutaneous, or central nervous system manifestations. All were managed with oral acyclovir, and had an uncomplicated recovery without neuralgia. By contrast, of 74 consecutive patients transplanted before use of MMF, only 1 patient (1.4%) had varicella infection after transplantation (P=0.026). CONCLUSION: The enhanced immunosuppression achieved with MMF appears to be associated with increased susceptibility to varicella infection.

Adolescent↗
PubMed1999

Hyperoxaluria and urolithiasis in young children: an atypical presentation.

Urolithiasis is uncommon in adolescence and rare in early childhood. In pediatric populations, congenital urinary tract anomalies associated with stasis and infection, idiopathic urolithiasis (adolescents), and nephrocalcinosis (premature infants) account for the majority of urolithiasis patients. Inborn errors of metabolism, such as the primary hyperoxalurias, are rare causes of urolithiasis in childhood. We report six children (mean age at symptom onset 1.3 years; range 0.32-4.1 years) with moderate hyperoxaluria (mean 1.10 +/- 0.58 mmoL/1.73m2 per day; range 0.69-2.19 mmoL/1.73m2 per day). Urolithiasis was present in four. Stones from two children were comprised of calcium oxalate dihydrate. Calcium oxalate crystalluria was seen in two of the patients. Findings included a mean urine calcium concentration of 6.61 +/- 2.28 mg/kg per day, urine citrate of 925.5 +/- 291.29 mg/g of creatinine per day, and mean renal clearance of 99.83 +/- 23.27 mL/min. All children were born full term, none was receiving diuretics, and none had recurrent urinary tract infections. Secondary causes of hyperoxaluria, including dietary oxalate excess, pyridoxine deficiency, and malabsorption, were excluded. Urine glycolate and glycerate were normal in all patients. In one hyperoxaluric member of each sibship, hepatic alanine-glyoxylate aminotransferase and D-glycerate dehydrogenase/glyoxylate reductase activity were normal. The clinical and biochemical features of these children are unlike those in previously recognized hyperoxaluric states. Thus, our description of a separate hyperoxaluric entity, referred to as unclassified hyperoxaluria.

Calcium Oxalate↗
PubMed1999

The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II.

Primary hyperoxaluria type II (PH2) is a rare monogenic disorder that is characterized by a lack of the enzyme that catalyzes the reduction of hydroxypyruvate to D-glycerate, the reduction of glyoxylate to glycolate and the oxidation of D-glycerate to hydroxypyruvate. The disease is characterized by an elevated urinary excretion of oxalate and L-glycerate. The increased oxalate excretion can cause nephrolithiasis and nephrocalci-nosis and can, in some cases, result in renal failure and systemic oxalate deposition. We identified a glyoxylate reductase/hydroxypyruvate reductase (GRHPR) cDNA clone from a human liver expressed sequence tag (EST) library. Nucleotide sequence analysis identified a 1198 nucleotide clone that encoded a 984 nucleotide open reading frame. The open reading frame encodes a predicted 328 amino acid protein with a mass of 35 563 Da. Transient transfection of the cDNA clone into COS cells verified that it encoded an enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Database analysis of human ESTs reveals widespread tissue expression, indicating that the enzyme may have a previously unrecognized role in metabolism. The genomic structure of the human GRHPR gene was determined and contains nine exons and eight introns and spans approximately 9 kb pericentromeric on chromosome 9. Four PH2 patients representing two pairs of siblings from two unrelated families were analyzed for mutations in GRHPR by single strand conformation polymorphism analysis. All four patients were homozygous for a single nucleotide deletion at codon 35 in exon 2, resulting in a premature stop codon at codon 45. The cDNA that we have identified represents the first characterization of an animal GRHPR sequence. The data we present will facilitate future genetic testing to confirm the clinical diagnosis of PH2. These data will also facilitate heterozygote testing and prenatal testing in families affected with PH2 to aid in genetic counseling.

Alcohol Oxidoreductases↗
PubMed1997

Neonatal presentation of autosomal dominant polycystic kidney disease with a maternal history of tuberous sclerosis.

BACKGROUND: Childhood presentation of polycystic kidney disease has been reported with tuberous sclerosis complex (TSC). Recently some such cases have been shown to be due to combined deletion of the PKD1 and TSC2 genes, which lie close together on chromosome 16. The phenomenon of anticipation, whereby disease presentation occurs at a progressively earlier age in each generation, has been suggested to occur in autosomal dominant polycystic kidney disease (ADPKD). We have carried out a genetic study of a family in which these issues became clinically relevant. Neonatal presentation of polycystic kidneys occurred in an individual with a maternal family history of epilepsy and features of TSC without renal cystic disease. METHODS: Detailed historical and clinical profiles were gathered for three generations of the maternal and paternal families. Both parents underwent renal ultrasound scanning. Genomic DNA was obtained from affected and unaffected individuals from the maternal family and used for linkage analysis to gene loci for TSC. RESULTS: Renal cysts were not present in the mother by ultrasound. Linkage to TSC2 was found for members of the maternal family with clinical features of TSC. While a diagnosis of TSC was confirmed in her mother the child was found not to have inherited the disease-related allele. The father was found to have asymptomatic bilateral polycystic kidneys consistent with ADPKD. The presence of ADPKD in other paternal relatives could not be confirmed. CONCLUSIONS: The index case was found to have paternally inherited ADPKD with unusually early presentation. While at risk for concomitant maternal inheritance of TSC this diagnosis was ruled out by linkage analysis studies. The ability to clarify the true nature of a complex inherited condition greatly facilitates future management and counselling. The mechanisms underlying phenotypic heterogeneity in ADPKD remain to be clearly defined and are the subject of ongoing investigation.

Female↗
PubMed1997

Extraction of glyceric and glycolic acids from urine with tetrahydrofuran: utility in detection of primary hyperoxaluria.

Primary hyperoxaluria (PH) is an autosomal recessive metabolic abnormality characterized by excessive oxalate excretion leading to nephrocalcinosis and progressive renal dysfunction. Type I primary hyperoxaluria (PH I) results from a deficiency of alanine:glyoxylate aminotransferase, whereas type II disease has been traced to a deficiency of D-glycerate dehydrogenase. The two syndromes are often distinguished on the basis of organic acids that are coexcreted with oxalate: glycolate and L-glycerate in type I and type II disease, respectively. Routine organic acid analysis with diethyl ether extraction followed by gas chromatographic analysis failed to detect normal and increased concentrations of these diagnostic metabolites. Subsequent extraction of urine with tetrahydrofuran (THF), however, extracted 75% of added glycerate, 42% of added glycolate, and 75% of added ethylphosphonic acid (internal calibrator). THF extraction was analytically sensitive enough to allow determination of normal excretion of glycolate (14-72 micrograms/mg creatinine) and glycerate (0-5 years, 12-177 micrograms/mg creatinine and > 5 years, 19-115 micrograms/mg creatinine). Four of five patients with PH I and both patients with type II disease were correctly identified. Thus, THF extraction is a convenient adjunct to routine organic acid analysis and facilitates the detection of PH.

Adolescent↗
PubMed1996

Ureteropelvic junction obstruction with concurrent renal pelvic calculi in the pediatric patient: a long-term followup.

PURPOSE: We determined the long-term prognosis of the pediatric patient presenting with simultaneous ureteropelvic junction obstruction and a renal calculus. MATERIALS AND METHODS: We retrospectively reviewed all individuals younger than 17 years who presented to our institutions with simultaneous ureteropelvic junction obstruction and an ipsilateral renal calculus. RESULTS: Simultaneous ureteropelvic junction obstruction with nonstruvite calculi was present in 22 patients, while 6 had struvite calculi. Median age at diagnosis was 11 years (range 5 to 16). During a median followup of 9 years (range 2 to 38) renal calculi recurred in 19 patients (68%), including 10 (36%) with 1 and 9 (32%) with 2 or more recurrences. Median time to first stone recurrence was 11 years (range 2 to 38). Of the 22 patients with nonstruvite calculi 15 (68%) had recurrence. An identifiable metabolic etiology for renal lithiasis was found in 13 of these patients (87%). In contrast, only 2 of the 7 patients (29%) with nonstruvite calculi and no recurrent stones had an identifiable abnormality. This finding suggests that the presence of an identifiable metabolic abnormality significantly predisposes to recurrent nonstruvite renal lithiasis (p < 0.01). CONCLUSIONS: Of the pediatric patients presenting with simultaneous ureteropelvic junction obstruction and a renal calculus 68% will have recurrent renal lithiasis. It remains to be determined whether active treatment of coexisting metabolic abnormalities could prevent or reduce the incidence of recurrent stone disease.

Adolescent↗
PubMed1995

An unusual renal complication in a patient with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a common 'rare' disorder with a reported incidence of 1/15,000 to 1/20,000 in newborns. Skeletal abnormalities in this condition are so striking that its equally important and diverse extraskeletal manifestations frequently remain unnoticed. Sensorineural deafness, blue sclerae, myopia, easy bruisability, dental anomalies, and floppy mitral valves are some of its more frequently reported extraskeletal features. Other less common features include pulmonary hypoplasia, joint contractures, hydrocephalus, and osteogenic sarcoma. Our patient, a 16-year-old boy, developed a previously unreported complication: chronic renal failure, which on subsequent evaluation was attributed to obstructive uropathy secondary to bony pelvic outlet deformities.

Acetabulum↗
PubMed1995

Urinary tract anomalies detected by prenatal ultrasound examination at Mayo Clinic Rochester.

OBJECTIVE: To determine the frequency of fetal urinary tract anomalies and to characterize the types of such abnormalities detected on ultrasonography and the outcome of affected patients during a 15-year period at our institution. DESIGN: We retrospectively reviewed the findings on maternal prenatal ultrasound examinations and the postnatal medical records of 56 children with urinary tract abnormalities detected by prenatal ultrasound examination at Mayo Clinic Rochester from November 1979 to June 1994. RESULTS: Of the 56 children, 18 (32%) had severe urinary tract anomalies in conjunction with oligohydramnios, pulmonary hypoplasia, and perinatal death (Potter's syndrome). The other 38 infants had various urinary tract abnormalities--most commonly, isolated hydronephrosis and multicystic dysplasia of the kidney. Six of the 38 children had more than one renal abnormality detected prenatally. Reflux was noted in association with prenatally detected urinary tract abnormalities in 4 of 32 newborns (12%) who underwent voiding cystourethrography. In fetuses with normal amniotic fluid volume, the perinatal outcome was good. Children with lower urinary tract obstruction had evidence of more severe renal dysfunction than did those with involvement at more proximal levels. The presence or absence of urinary tract obstruction postnatally could not be determined reliably on the basis of prenatal ultrasound appearance. CONCLUSION: In this study, more than half of all prenatally detected urinary tract abnormalities were isolated hydronephrosis or multicystic dysplasia of the kidney. Postnatal renal function could not be reliably predicted on the basis of prenatal ultrasound findings.

Female↗
PubMed1995

Ureteropelvic junction obstruction with a simultaneous renal calculus: long-term followup.

We reviewed 111 patients who presented with simultaneous renal calculi and a ureteropelvic junction obstruction. Of 34 patients with ureteropelvic junction obstruction and a coexisting struvite stone 62% had recurrent calculi. The use of antibiotics significantly affected the incidence of recurrent struvite calculi. In particular, if prolonged prophylactic antibiotics (greater than 3 months) were used 15% of the patients had recurrent stones, compared to 90% if only perioperative antibiotics (less than 15 days) were used (p < 0.001). Patients with ureteropelvic junction obstruction and coexisting nonstruvite calculi were treated by either observation alone (53) or metabolic evaluation with appropriate intervention (24). Metabolic evaluation of patients with nonstruvite calculi revealed that 76% had an identifiable metabolic abnormality, treatment of which significantly decreased the incidence of recurrent renal calculi: 17% of the patients on interventional therapy had recurrent stones compared to 55% treated by observation alone (p < 0.001).

Anti-Bacterial Agents↗
PubMed1994

Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria.

BACKGROUND: The prognosis for patients with primary hyperoxaluria has been ominous, with the expectation of renal failure, poor results with transplantation, and early death. METHODS: We studied the long-term effects of orthophosphate and pyridoxine therapy in 25 patients with primary hyperoxaluria who were treated for an average of 10 years (range, 0.3 to 26). Their mean age at the start of treatment was 12 years (median, 6; range, 0.5 to 32). We also studied the effect of orthophosphate and pyridoxine on urinary supersaturation with calcium oxalate, crystal inhibition using a seeded growth system, and crystal formation using scanning electron microscopy in 12 patients during three-day stays in the clinical research center. RESULTS: The mean (+/- SD) glomerular filtration rate at the start of treatment was 91 +/- 26 ml per minute per 1.73 m2. The median decline in glomerular filtration rates was 1.4 ml per minute per 1.73 m2 of body-surface area per year. The actuarial survival free of end-stage renal disease was 96, 89, 74, and 74 percent of 5, 10, 15, and 20 years, respectively. Treatment with orthophosphate and pyridoxine reduced urinary supersaturation with calcium oxalate from 8.3 +/- 3.0 to 2.1 +/- 1.7 kJ per mole at 38 degrees C (P < 0.001), increased the inhibition of calcium oxalate formation from 63 +/- 11 to 108 +/- 10 inhibitor units per 24 hours (P < 0.001), and improved the crystalluria score from 2.6 +/- 0.3 to 0.6 +/- 0.1 (P < 0.001). CONCLUSIONS: Treatment of patients with primary hyperoxaluria with orthophosphate and pyridoxine decreases urinary calcium oxalate crystallization and appears to preserve renal function.

Actuarial Analysis↗
PubMed1994

Effect of cyclosporine A on long-term allograft function in pediatric renal transplant recipients.

There have been concerns regarding long-term adverse effects of cyclosporine A (CSA) on renal allograft function. In a retrospective study, we compared long-term allograft function up to 70 months after renal transplantation in pediatric recipients treated with and without CSA, using iothalamate clearance to assess glomerular filtration rate. Patients received CSA, prednisone, and azathioprine (CSA group, n = 16) or prednisone and azathioprine alone (Pred/AZA, n = 11). At 48 months post transplant, the iothalamate clearances (mean +/- SD) were 57.9 +/- 26.8 ml/min per 1.73 m2 in the CSA group and 68.5 +/- 20.2 in the Pred/AZA group (P > 0.05). The mean of the slopes of individual iothalamate clearances versus time during the first 70 months following transplantation were -0.156 in the CSA group and 0.095 in the Pred/AZA group. Neither slope was statistically different from zero. These data suggest that allograft function is not significantly depressed by CSA at 48 months post transplantation and that there is no greater rate of decline in allograft function up to 70 months post transplantation in patients receiving CSA when compared with the AZA/Pred group.

Adolescent↗
PubMed1994

Long-term prognosis in primary hyperoxaluria type II (L-glyceric aciduria).

Primary hyperoxaluria type II (PH-II) or L-glyceric aciduria was first reported by Williams and Smith in 1968 (N Engl J Med 278:233-239, 1968). Deficiencies of D-glycerate dehydrogenase and glyoxylate reductase activity in patients with this disorder leads to increases in urinary oxalate and glycerate excretion. Clinically, PH-II presents in a similar fashion to the more common variant of the disorder, PH-I, with symptoms of calcium oxalate nephrolithiasis. To date, 16 patients with PH-II have been described, and information regarding follow-up is available in only three. We review these reports and present five additional patients from three families, four of whom have been followed closely for more than 20 years. The favorable long-term outcome of our patients over 110 patient-years, as determined by renal function testing and radiographic evaluation, suggests that PH-II may have a more favorable prognosis when compared with the natural history of PH-I. Systematic screening of all PH patients in our practice led to the discovery of five of 30 with PH-II, thus suggesting that this subset population may be more common than originally suspected.

Adolescent↗